Largest study of cognitive decline in patients with common neurodegenerative condition could improve counseling, treatment
Patients with a common movement disorder known as essential tremor (ET) developed dementia at three times the rate of similarly aged people in the general population, a study led by UT Southwestern Medical Center researchers shows. Their findings, published in the Annals of Neurology, provide the first concrete data to help doctors counsel those with this condition on their cognitive prognosis, future plans, and potential treatments, the authors said.
“In the past, these patients have been told, ‘You’re old, and that’s why you have these cognitive problems.’ Now we can tell patients with confidence that this is part of their disease,” said Elan Louis, M.D., M.S., Chair and Professor of Neurology and in the Peter O’Donnell Jr. School of Public Health at UT Southwestern. Dr. Louis, an Investigator in the Peter O’Donnell Jr. Brain Institute, initiated and co-led the study with Stephanie Cosentino, Ph.D., Professor of Neuropsychology at Columbia University.
Elan Louis, M.D., M.S., Chair and Professor of Neurology and in the Peter O'Donnell Jr. School of Public Health at UT Southwestern, is an Investigator in the Peter O’Donnell Jr. Brain Institute. Dr. Louis holds the Linda and Mitch Hart Distinguished Chair in Neurology.
ET is the second-most common neurodegenerative disease worldwide, affecting about 7 million people in the U.S. with about 1,000 new diagnoses every day, Dr. Louis explained. Although this condition can arise at all ages, it is most common in older adults. Marked by rhythmic trembling of the hands, head, and/or trunk, ET is often accompanied by nonmotor features such as anxiety and depression, hearing impairment, and sleep difficulties.
A handful of studies have suggested cognitive impairment can also be part of this disease. The new study assessed a range of cognitive metrics in the largest group of ET patients tracked for the longest time so far, providing the most complete data to date.
The study followed 222 ET patients with a mean age of 79 for an average of five years starting in July 2014. At baseline, and then at 18-month intervals, a trained research aide visited the patients at home to administer a comprehensive battery of neuropsychological tests that measured cognitive function in five broad areas. These included attention, executive function, language, memory, and visuospatial ability – such as recognizing faces or solving visual puzzles.
The tests showed that nearly 16% of participants began with mild cognitive impairment (MCI), and about 9% had dementia. Using data from 177 patients who remained in the study after some had dropped out or passed away, the cumulative prevalence of MCI was nearly 27%, and the cumulative prevalence of dementia was almost 19%. Further analysis showed that every year during the study period, about 4% of participants who had no cognitive impairment at the start developed MCI and about 12% of those with MCI developed dementia. Both the annual conversion rate of MCI to dementia and the cumulative prevalence of dementia were three times higher than in the general population, Dr. Louis said.
These findings have significant ramifications for patients and their families, he added. Previous studies have shown that ET patients with dementia are more likely to use a walker or wheelchair, to employ a home health aide, and to have nonindependent living arrangements than ET patients without dementia. Dementia also doubles ET patients’ risk of death.
By knowing these risks, doctors can better counsel patients, help them plan, and potentially prescribe therapies recently approved or in development to treat cognitive decline, Dr. Louis said. He and his colleagues are studying donated brains of ET patients to better understand how this decline develops and progresses. Studies in the works will search patients’ blood for biomarkers that could predict who will develop dementia and investigate whether cognitive decline might precede motor symptoms in patients ultimately diagnosed with ET. The team also is investigating other potential predictors of cognitive decline in ET – for example, another recent study led by Dr. Louis showed that longer sleep latency (the time it takes a person to fall asleep) was a significant predictor of which ET patients developed cognitive impairments.
Other UTSW researchers who contributed to the ET/dementia study include first author Ali Ghanem, M.D., M.S., Research Study Coordinator in the Louis Lab; Vibhash Sharma, M.D., Associate Professor of Neurology and Medical Director for the Interventional (Neuromodulation) Movement Disorders clinic; Diane S. Berry, Ph.D., Biostatistical Consultant; Natalie Grill, B.S., and Talia M. Hall, B.A., Clinical Research Coordinators; and Nora C. Hernandez, M.D., Manager of Research Programs.
Dr. Louis holds the Linda and Mitch Hart Distinguished Chair in Neurology.
This study was funded by a grant from the National Institutes of Health (R01 NS086736).